Technical Field
The present disclosure relates to gold(III) complexes with anti-cancer activity and a method of treating cancer.
Description of the Related Art
The “background” description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description which may not otherwise qualify as prior art at the time of filing, are neither expressly or impliedly admitted as prior art against the present invention.
One of the most important areas of study in contemporary bioinorganic chemistry is the development of new metal-based drugs (S. L. Best and P. J. Sadler, Gold Bull., vol. 29, no. 3, pp. 87-93, 1996; A. Casini, G. Kelter, C. Gabbiani, M. A. Cinellu, G. Minghetti, D. Fregona, H.-H. Fiebig, and L. Messori, J. Bio. Inorg. Chem., vol. 14, no. 7, pp. 1139-1149, 2009; S. H. van Rijt and P. J. Sadler, Drug Discov. Today, vol. 14, no. 23-24, pp. 1089-97, 2009; X. Wang and Z. Guo, Dalton Trans., no. 12, pp. 1521-32, 2008; C. Frank Shaw III, Chem. Rev., vol. 99, no. I, pp. 2589-2600, 1999; P. J. Sadler and R. E. Sue, Met. Based Drugs, vol. 1, pp. 107-44, 1994; I. Ott, Coord. Chem. Rev., vol. 253, no. 11-12, pp. 1670-1681, 2009; A. C. and L. M. Chiara Gabbiani, Gold Bull, vol. 40, pp. 73-81, 2007; M. A. Cinellu, L. Maiore, M. Manassero, A. Casini, M. Arca, H.-H. Fiebig, G. Kelter, E. Michelucci, G. Pieraccini, C. Gabbiani, and L. Messori, ACS Med Chem. Lett., vol. 1, no. 7, pp. 336-339, 2010; and A. Bindoli, M. P. Rigobello, G. Scutari, C. Gabbiani, A. Casini, and L. Messori, Coord. Chem. Rev., vol. 253, no. 11-12, pp. 1692-1707, 2009, each incorporated herein by reference in their entirety). Despite the successful use of cisplatin as a chemotherapy agent, side effects and resistance have been observed (A. Casini, C. Hartinger, C. Gabbiani, E. Mini, P. J. Dyson, B. K. Keppler, and L. Messori, J. Inorg. Biochem., vol. 102, no. 3, pp. 564-575, 2008; and V. Milacic, D. Fregona, and Q. P. Dou, Histol. Histopathol., vol. 23, no. 1, pp. 101-108, 2008, each incorporated herein by reference in their entirety). The use of gold in anti-rheumatic treatment supports its pharmaceutical importance (M. W. Whitehouse, Inflammopharmacology, vol. 16, no. 3, pp. 107-9, 2008; G. G. Graham, M. W. Whitehouse, and G. R. Bushell, Inflammopharmacology, vol. 16, no. 3, pp. 126-32, 2008; A. Casini, M. A. Cinellu, G. Minghetti, C. Gabbiani, M. Coronnello, E. Mini, and L. Messori, J. Med. Chem., vol. 49, no. 18, pp. 5524-31, 2006; and L. Ronconi, L. Giovagnini, C. Marzano, F. Bette, R. Graziani, G. Pilloni, and D. Fregona, Inorg. Chem., vol. 44, no. 6, pp. 1867-81, 2005, each incorporated herein by reference in their entirety). Recent studies have shown that several gold(III) complexes are highly cytotoxic against different tumor cells (L. Giovagnini, L. Ronconi, D. Aldinucci, D. Lorenzon, S. Sitran, and D. Fregona, J. Med. Chem., vol. 48, no. 5, pp. 1588-95, 2005; A. Casini, M. A. Cinellu, G. Minghetti, C. Gabbiani, M. Coronnello, E. Mini, and L. Messori, J. Med. Chem., vol. 49, no. 18, pp. 5524-5531, 2006; and D. Saggioro, M. P. Rigobello, L. Paloschi, A. Folda, S. A Moggach, S. Parsons, L. Ronconi, D. Fregona, and A. Bindoli, Chem. Biol., vol. 14, no. 10, pp. 1128-39, 2007, S. S. Al-Jaroudi, M. Monim-ul-Mehboob, M. Altaf, M. Fettouhi, M. I. M. Wazeer, S. Altuwaijri, and A. A. Isab, New J. Chem., vol 38, pp. 3199-3211, 2014; M. Arsenijevic, M. Milovanovic, V. Volarevic, A. Djekovic, T. Kanjevac, N. Arsenijevic, S. Dukic, Z. D. Bugarcic, Med. Chem., vol. 8, no. 1, pp. 2-8, 2012, each incorporated herein by reference in their entirety). Oxaliplatin, a platinum-based drug, is coordinated to (1R,2R)-(−)-1,2-diaminocyclohexane and a labile oxalate ligand (G. Sava, A. Bergamo, and P. J. Dyson, Dalton Trans., vol. 40, no. 36, pp. 9069-75, 2011; and L. Kelland, Nat. Rev. Cancer, vol. 7, no. 8, pp. 573-84, 2007, each incorporated herein by reference in their entirety).
Interactions of gold(III) complexes with biomolecules, such as sulfur-containing amino acids, thiols, or thioethers, are thought to be the cause of the cytotoxic effect of gold(III) complexes (A. V. Vuja{hacek over (c)}ić, J. Z. Savić, S. P. Sovilj, K. Mészáros Szécsényi, N. Todorović, M. {hacek over (Z)}. Petković, and V. M. Vasić, Polyhedron, vol. 28, no. 3, pp. 593-599, 2009, incorporated herein by reference in its entirety). The toxic effects arise due to the coordination of the thiol and thioether groups of the side chains in proteins, peptides and amino acids followed by the reduction of gold(III) to gold(I) and subsequently to toxic gold(0) (T. Kolev, B. B. Koleva, S. Y. Zareva, and M. Spiteller, Inorg. Chien. Acta, vol. 359, no. 13, pp. 4367-4376, 2006; J. Zou, Z. Guo, J. A. Parkinson, Y. Chen, and P. J. Sadler, Chem. Commun., vol. 8, pp. 1359-1360, 1999; J. A. Cuadrado, W. Zhang, W. Hang, and V. Majidi, J. Env. Monit, vol. 2, no. 4, pp. 355-359, 2000; and P. L. Witkiewicz. and C. F. Shaw. III, J. Chem. Soc. Chem. commun, pp. 1111-1114, 1981, each incorporated herein by reference in their entirety). The electrochemistry of the interaction of guanosine-5-phosphate with gold(III) ethylenediamine complexes was studied by Zhu et al. (S. Zhu, W. Gorski, D. R. Powell, and J. A. Walmsley, Inorg. Chem., vol. 45, no. 6, pp. 2688-2694, 2006, incorporated herein by reference in its entirety). The interaction of the dipeptide Gly-Met with gold(III) ethylenediamine showed the formation of Gly-Met sulfoxide along with a free ethylenediamine ligand through a two-step decomposition reaction (B. . Gli{hacek over (s)}ić, M. I. Djuran, Z. D. Stanić, and S. Rajković, Gold Bull, vol. 47, no. 1-2, pp. 33-40, 2014, incorporated herein by reference in its entirety). The substitution and reduction steps for the reaction of some gold(III) complexes with the biological thiols, L-cysteine, L-methionine, and glutathione were studied in detail by Durović et al. (M. D. Durović, Z. D. Bugar{hacek over (c)}ić, F. W. Heinemann, and R. van Eldik, Dalton. trans., vol. 43, no. 10, pp. 3911-21, 2014, incorporated herein by reference in its entirety). The interaction between [Au(CN)4]− and glutathione (GSH) at pH 7.4 showed the reduction of gold(III) to gold(I) along with the dimerization of GSH into its disulfide (GSSG2−) derivative as the reaction product through a two-step decomposition reaction (P. M. Yangyuoru, J. W. Webb, and C. F. Shaw, J. Inorg. Biochem., vol. 102, no. 3, pp. 584-93, 2008; and B. A. Al-Maythalony, M. I. M. Wazeer, and A. A. Isab, Inorg. Chim. Acta, vol. 363, no. 13, pp. 3244-3253, 2010, each incorporated herein by reference in their entirety).
Therefore, it is an objective of this disclosure to provide gold(III) complexes with anti-cancer activity and a method for treating cancer.